We shall make definitive measurements of the respiratory activity of phagocytic leukocytes during phagocytosis, and their production of O2 and H2O2, made possible now by the development of new methods. These measurements will be make on guinea pig neutrophilic granulocytes, elicited macrophages and alveolar macrophages, the same cells taken from mice and rats, and also resident peritoneal macrophages in mice as well as activated macrophages. Many of the data are already in hand. We should resolve the question of the mechanism of respiratory stimulation in the neutrophilic granulocytes - a real possibility now that the reduced tri-phospho pyridine nucleotide oxidase has been shown to be artefactual. In particular, we shall study the mode of activation of the membrane-bound NADH-oxidase and its role in the phagosome, in which it appears to be considerably activated. We shall continue to explore the ectoenzymes of phagocytic leukocytes by enlarging the number of enzymes recognized as such. This serine esterase that has been implicated in complement-related reactions in chemotaxis will be further explored with respect to its cytological location in granulocytes, and in macrophages in which it appears in much greater concentrations. The mechanism by means of which such agents as MIF activate macrophages will be determined by measurement of macrophage enzymes and metabolic chracteristics additional to those already examined, after exposure of the cells to MIF. We shall look at the biochemical lesion in bacteria killed by exposure to peroxide:peroxidase:halide, or peroxide: ascorbate:metal systems. BIBLIOGRAPHIC REFERENCES: Karnovsky, M. L.: "Biochemical aspects of the functions of polymorphonuclear and mononuclear leukocytes" in The Phagocytic Cell in Host Resistance, eds. J. A. B ellanti and D.H. Dayton, Raven Press, New York. 1975, pp. 25-43. Briggs, R.T., Karnovsky, M.L. and Karnovsky, M.J.: Cytochemical demonstration of hydrogen peroxide in polymorphonuclear leukocyte phagosomes. J. Cell Biol. 64: 254-260, 1975.